1. Field of the Invention
This invention concerns novel derivatives of certain bicyclo[4.2.0]octanes and pharmaceutically acceptable salts and esters thereof, and in particular their use in treating gastrointestinal and cardiovascular disorders. The invention also relates to pharmaceutical compositions containing these compounds, and methods of preparing such compounds.
2. Related Disclosures
The synthesis of certain bicyclo[4.2.0]octane derivatives, useful for treating cardiovascular disorders, was disclosed in U.S. Pat. Nos. 4,608,388, 4,678,805 and 4,735,966, the relevant portions of which are hereby incorporated by reference.
Several prostaglandin analogues are known which contain bicyclic all-carbon skeletons. Carbacyclin contains a bicyclo[3.3.0]octane skeleton, and is described in several publications (J. Chem. Soc., Chem. Commun., 1067, 1978, Tetrahedron Lett., 3743, 1978; Tetrahedron Lett., 433, 1979; Tetrahedron Lett., 2807, 1979; J. Org. Chem. 44:2880, 1979) and patents (for example U.S. Pat No. 4,238,414). Numerous analogues of carbaprostacyclin are described (U.S. Pat. No. 4,306,076; Ger. Offen. Nos. 3,146,278; 3,204,443; Prostaglandins, Leukotrienes Med., 9:307, 1982; J. Org. Chem. 48, 5341, 1983; Tetrahedron Lett. 3493, 1983; Biochem. Pharmacol. 32:2405, 1983; Prostaglandins, Leukotrienes. Med. 11:391, 1983). 9-Substituted analogs of carbacyclin are described in U.S. Pat. Nos. 4,487,960 and 4,487,961.
Synthetic prostaglandins (homo PGE.sub.2 and homo PGF.sub.2.alpha.) have been prepared with the hydroxyl function and lower side chain trans-opposed in a 6-membered ring (Tetrahedron Lett., 3327, 1971).